TNFα modulates fas/fasl induced cell death and immune deviation in the eye

Y. Gao, J. M. Herndon, T. S. Griffith, T. A. Ferguson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose. The eye expresses FasL which induces apoptosis in invading Fas' inflammatory cells This apoptotic celt death is critical to the induction of immune deviation following AC injection of antigen. Here we examine the role of TNFa in the FasL-induced cell death in the eye leading to the induction of immune deviation. Methods C57BL/6 (B6), B6-TNFR-1 KO, B6-TNFR-2 KO mice were injected in the anterior chamber (AC) with TNP-spl. Mice were examined for immune deviation, and the eyes were assessed for the presence of apoptotic cells by in situ TUNEL stains. Lymphoid cells were incubated with TNFa and then tested for susceptibility to Fasmediated death Results. TNFa mRNA and protein are made within 90 min of injection of antigen into the AC, but returns to normal within 4 hrs. Co-injection of anti-TNFa blocked apoptosis of cells in the eye and prevented immune deviation. TNPspl from TNFR-1 KO undergo apoptosis and induce immune deviation when injected into the eyes of B6, but not B6-gld mice, while TNFR-2 KO TNP-spl do not. Using normal lymphocytes from B6 spleen and a T-cell hybridoma, we show that preincubation of these cells with TNFa does not result in apoptosis, but makes these celts susceptible to death induced by FasL. Conclusions. Our results suggest that TNFa signaling through the TNFR-2 receptor, participates in FasL-induced apoptosis in the eye by "sensitizing" lymphoid cells for killing by Fas These results also provide further evidence for the essential role of apoptotic cell death in the eye for the establishment of immune deviation, as well as the complicity between elements of the inflammatory response in the maintenance of immune privilege by FasL Supported by NIH grants EY06765 and EY02687. None.

Original languageEnglish (US)
Pages (from-to)S183
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
StatePublished - Dec 1 1997

Fingerprint Dive into the research topics of 'TNFα modulates fas/fasl induced cell death and immune deviation in the eye'. Together they form a unique fingerprint.

Cite this